铁催化下二芳基锌和芳基格氏试剂的二氟烷基化反应

doi:10.6023/A18080314

化学学报 ›› 2018, Vol. 76 ›› Issue (12): 977-982.DOI: 10.6023/A18080314 上一篇下一篇

所属专题：有机氟化学

研究通讯

铁催化下二芳基锌和芳基格氏试剂的二氟烷基化反应

安伦, 童非非, 张新刚

中国科学院上海有机化学研究所分子合成卓越中心中国科学院有机氟化学重点实验室上海 200032

投稿日期:2018-09-18 发布日期:2018-12-11
通讯作者: 张新刚,E-mail:xgzhang@sioc.ac.cn,Tel.:021-54925333,Fax:021-64166128 E-mail:xgzhang@sioc.ac.cn
基金资助:
项目受国家重点基础研究发展计划（973计划）（No.2015CB931900）、国家自然科学基金（Nos.21425208，21672238，21332010，21421002）和中国科学院先导专项（No.XDB20000000）资助.

Iron-Catalyzed Cross-Coupling of Diarylzinc or Aryl Grignard Reagents with Difluoroalkyl Bromides

An Lun, Tong Feifei, Zhang Xingang

Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Received:2018-09-18 Published:2018-12-11
Contact: 10.6023/A18080314 E-mail:xgzhang@sioc.ac.cn
Supported by:
Project supported by the National Basic Research Program of China (973 Program) (No. 2015CB931900), the National Natural Science Foundation of China (Nos. 21425208, 21672238, 21332010 and 21421002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB20000000).

文章分享

1. 铁催化下二芳基锌和芳基格氏试剂的二氟烷基化反应.PDF(3678KB)

摘要/Abstract

随着医药、农药、材料等领域对含氟化合物日益增长的需求，发展向有机分子中直接引入氟原子和含氟基团的方法受到了化学家们的广泛重视.近些年来，过渡金属催化的氟烷基化反应，作为一种温和可控向有机分子引入含氟基团的策略得到了快速发展.与此同时，从反应的高效简洁和绿色温和性角度出发，发展廉价金属作为催化剂以及使用廉价易得的氟卤烷烃作为氟烷基试剂是非常具有吸引力的.本文以绿色低毒的Fe（acac）₃为催化剂，首次实现了铁催化下二芳基锌与α，α-二氟炔丙基溴的交叉偶联反应.该反应条件温和、原料廉价易得，产物可以放大到克量级制备，并能进行多种转化.此外，这一铁催化体系还可以实现芳基格氏试剂与二氟烷基溴代的偶联反应，为合成二氟烷基芳烃化合物提供了一种有效方法.初步的机理研究表明，该反应可能经历了单电子转移的自由基反应历程，偕二氟炔丙基自由基存在反应催化循环中.

关键词: 铁, 二芳基锌试剂, α,α-二氟炔丙基溴, 交叉偶联反应

The demanding of discovering new pharmaceuticals, agrochemicals and advanced functional materials have triggered extensive efforts on efficient synthesis of fluorinated compounds. Over the past decade, the transition-metal-catalyzed fluoroalkylation has emerged as an efficient and straightforward strategy for the synthesis of organofluorine compounds. Despite the importance of the reported synthetic methods, the development of environmentally benign and cost-efficient fluoroalkylation reactions with base metals as catalysis and widely available fluoroalkyl halides as fluoroalkyl sources continues to attract great interest. Here, we reported the first example of iron-catalyzed cross-coupling of diarylzinc reagents with gem-difluoropropargyl bromides. The reaction proceeds under mild reaction conditions and provides a facile access to gem-difluoropropargyl arenes. Additionally, this iron-catalytic system can also be applied to the cross-coupling of aryl Grignard reagents with difluoroalkyl bromides. Applications of the method led to modified bioactive molecules efficiently, offering potential opportunities in medicinal chemistry. Preliminary mechanistic studies reveal that a single electron transfer pathway is involved in the reaction. A representative procedure for iron-catalyzed cross-coupling of diarylzincs with gem-difluoropropargyl bromide is as following: Fe(acac)₃ (10 mol%) was added to a 25 mL of Schlenck tube, the tube was then evacuated and backfilled with Ar (3 times). gem-Difluoropropargyl bromide 2 (0.3 mmol, 1.0 equiv.), TMEDA (0.45 mmol, 1.5 equiv.) and THF (1 mL) were then added, the reaction mixture was stirred at room temperature for 10 min and cooled to -20 ℃. A solution of diarylzinc reagent (0.45 mmol in 1.5 mL of THF, 1.5 equiv.) was added dropwise. After stirring for 4 h at -20 ℃, the reaction mixture was quenched with saturated NH₄Cl solution. The yield was determined by ¹⁹F NMR before working up. If necessary, the reaction mixture was diluted with EtOAc and filtered with a pad of cellite. The filtrate was concentrated, and the residue was purified with silica gel chromatography to give product 3.

Key words: iron, diarylzinc reagents, gem-difluoropropargyl bromide, cross-coupling

引用此文

安伦, 童非非, 张新刚. 铁催化下二芳基锌和芳基格氏试剂的二氟烷基化反应[J]. 化学学报, 2018, 76(12): 977-982.

An Lun, Tong Feifei, Zhang Xingang. Iron-Catalyzed Cross-Coupling of Diarylzinc or Aryl Grignard Reagents with Difluoroalkyl Bromides[J]. Acta Chim. Sinica, 2018, 76(12): 977-982.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

参考文献

[1] For selected reviews, see:(a) Hiyama, T. Organofluorine Compounds, Chemistry and Applications, Springer-Verlag, Berlin Heidelberg, 2000.
(b) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881.
(c) O' Hagan, D. Chem. Soc. Rev. 2008, 37, 308.
(d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.
[2] (a) Blackburn, C. M.; England, D. A.; Kolkmann, F. J. Chem. Soc. Chem. Commun. 1981, 930.
(b) Blackburn, G. M.; Kent, D. E.; Kolkmann, F. J. Chem. Soc., Perkin Trans. 1 1984, 1119.
(c) Kitazume, T.; Kamazaki, T. Experimental Methods in Organic Fluorine Chemistry, Gordon and Breach Science, Tokyo, 1998.
(d) Yang, Y.; You, Z.; Qing, F.-L. Acta Chim. Sinica 2012, 70, 2323(in Chinese). (杨义, 游正伟, 卿凤翎, 化学学报, 2012, 70, 2323.)
[3] For selected reviews, see:(a) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529.
(b) Meanwell, N. A. J. Med. Chem. 2018, 61, 5822.
[4] For selected examples, see:(a) Xue, F.; Li, H.; Delker, S. L.; Fang, J.; Martasek, P.; Roman, L. J.; Poulos, T. L.; Silverman, R. B. J. Am. Chem. Soc. 2010, 132, 14229.
(b) Anderson, M. O.; Zhang, J.; Liu, Y.; Yao, C.; Phuan, P.-W.; Verkman, A. S. J. Med. Chem. 2012, 55, 5942.
(c) Matthew, A. N.; Zephyr, J.; Hill, C. J.; Jahangir, M.; Newton, A.; Petropoulos, C. J.; Huang, W.; Kurt-Yilmaz, N.; Schiffer, C. A.; Ali, A. J. Med. Chem. 2017, 60, 5699.
[5] (a) Markovsi, L. N.; Pahinnik, V. E.; Kirsanov, A. V. Synthesis 1973, 12, 787.
(b) Middleton, W. J. J. Org. Chem. 1975, 40, 574.
[6] For selected reviews regarding fluorination and trifluoromethylation, see:(a) Furuya, T.; Kamlet, A. S.; Ritter, T. Nature 2011, 473, 470.
(b) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111, 4475.
[7] For transition-metal-catalyzed difluoroalkylation, see:(a) Chen, B.; Vicic, D. A. Top. Organomet. Chem. 2014, 52, 113.
(b) Ni, C.; Zhu, L.; Hu, J. Acta Chim. Sinica 2015, 73, 90(in Chinese). (倪传法, 朱林桂, 胡金波,化学学报, 2015, 73, 90.)
(c) Wang, W.; Yu, Q.; Zhang, Q.; Li, J.; Hui, F.; Yang, J.; LÜ, J. Chin. J. Org. Chem. 2018, 38, 1569(in Chinese). (王为强, 余秦伟, 张前, 李江伟, 惠丰, 杨建明, 吕剑, 有机化学, 2018, 38, 1569.)
[8] (a) McLoughlin, V. C. R.; Thrower, J. Tetrahedron 1969, 25, 2921.
(b) Kobayashi, Y.; Kumadaki, I. Tetrahedron Lett. 1969, 10, 4095.
(c) Taguchi, T.; Kitagawa, O.; Morikawa, T.; Nishiwaki, T.; Uehara, H.; Endo, H.; Kobayashi, Y. Tetrahedron Lett. 1986, 27, 6103.
[9] (a) Chen, Q.-Y.; Yang, Z.-Y. J. Fluorine Chem. 1985, 28, 399.
(b) Chen, Q.-Y.; Yang, Z.-Y. Acta Chim. Sinica 1985, 43, 1118(in Chinese). (陈庆云, 杨振宇, 化学学报, 1985, 43, 1118.)
(c) Zhou, Q.-L.; Huang, Y.-Z. J. Fluorine Chem. 1989, 43, 385.
(d) Huang, W.-Y. Youji Huaxue, 1992, 12, 12(in Chinese). (黄维垣, 有机化学, 1992, 12, 12)
(e) Huang, X.-T.; Long, Z.-Y.; Chen, Q.-Y. J. Fluorine Chem. 2001, 111, 107.
[10] (a) Feng, Z.; Xiao, Y.-L.; Zhang, X. Acc. Chem. Res. 2018, 51, 2264.
(b) Feng, Z.; Chen, F.; Zhang, X. Org. Lett. 2012, 14, 1938.
(c) Min, Q.-Q.; Yin, Z.; Feng, Z.; Guo, W.-H.; Zhang, X. J. Am. Chem. Soc. 2014, 136, 1230.
(d) Feng, Z.; Min, Q.-Q.; Xiao, Y.-L.; Zhang, B.; Zhang, X. Angew. Chem., Int. Ed. 2014, 53, 1669.
(e) Xiao, Y.-L.; Guo, W.-H.; He, G.-Z.; Pan, Q.; Zhang, X. Angew. Chem., Int. Ed. 2014, 53, 9909.
(f) Feng, Z.; Min, Q.-Q.; Fu, X.-P.; An, L.; Zhang, X. Nat. Chem. 2017, 9, 918.
(g) An, L.; Xu, C.; Zhang, X. Nat. Commun. 2017, 8, 1460.
[11] For selected reviews, see:(a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217.
(b) Sherry, B. D.; FÜrstner, A. Acc. Chem. Res. 2008, 41, 1500.
(c) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417.
(d) Nakamura, E.; Hatakeyama, T.; Ito, S.; Ishizuka, K.; Ilies, L.; Nakamura, M. Org. React. 2014, 83, 1.
(e) Bauer, I.; Knölker, H.-J. Chem. Rev. 2015, 115, 3170.
(f) Kuzmina, O. M.; Steib, A. K.; Moyeux, A.; Cahiez, G.; Knochel, P. Synthesis 2015, 47, 1696.
(g) Bedford, R. B. Acc. Chem. Res. 2015, 48, 1485.
(h) Mako, T. L.; Byers, J. A. Inorg. Chem. Front. 2016, 3, 766.
(i) Shang, R.; Ilies, L.; Nakamura, E. Chem. Rev. 2017, 117, 9086.
[12] For an iron-catalyzed cross-coupling of a-halo-b,b-difluoroethylene-containing compounds, see:(a) Lin, X.; Zheng, F.; Qing, F.-L. Organometallics 2012, 31, 1578. For an iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone, see:(b) Miao, W.; Zhao, Y.; Ni, C.; Gao, B.; Zhang, W.; Hu, J. J. Am. Chem. Soc. 2018, 140, 880.
[13] An, L.; Xiao, Y.-L.; Zhang, X. Angew. Chem., Int. Ed. 2018, 57, 6921.
[14] Xu, B.; Mashuta, M. S.; Hammond, G. B. Angew. Chem., Int. Ed. 2006, 45, 7265.
[15] (a) Yu, Y.-B.; He, G.-Z.; Zhang, X. Angew. Chem., Int. Ed. 2014, 53, 10457.
(b) Guo, W.-H.; Luo, Z.-J.; Zeng, W.; Zhang, X. ACS Catal. 2017, 7, 896.
(c) Xiao, Y.-L.; Pan, Q.; Zhang, X. Acta Chim. Sinica 2015, 73, 383(in Chinese). (肖玉兰, 潘强, 张新刚, 化学学报, 2015, 73, 383.)
[16] (a) Furstner, A.; Martin, R.; Krause, H.; Seidel, G.; Goddard, R.; Lehmann, C. W. J. Am. Chem. Soc. 2008, 130, 8773.
(b) Noda, D.; Sunada, Y.; Hatakeyama, T.; Nakamura, M.; Nagashima, H. J. Am. Chem. Soc. 2009, 131, 6078.
(c) Bedford, R. B.; Brenner, P. B.; Carter, E.; Cogswell, P. M.; Haddow, M. F.; Harvey, J. N.; Murphy, D. M.; Nunn, J.; Woodall, C. H. Angew. Chem., Int. Ed. 2014, 53, 1804.
[17] (a) Hedstrçm, A.; Izakian, Z.; Vreto, I.; Wallentin, C.-J.; Norrby, P. Chem. Eur. J. 2015, 21, 5946;
(b) Daifuku, S. L.; Kneebone, J. L.; Snyder, B. E. R.; Neidig, M. L. J. Am. Chem. Soc. 2015, 137, 11432;
(c) Kneebone, J. L.; Brennessel, W. W.; Neidig, M. L. J. Am. Chem. Soc. 2017, 139, 6988.
[18] (a) Sharma, A. K.; Sameera, W. M. C.; Jin, M.; Adak, L.; Okuzono, C.; Iwamoto, T.; Kato, M.; Nakamura, M.; Morokuma, K. J. Am. Chem. Soc. 2017, 139, 16126.
(b) Lee, W.; Zhou, J.; Gutierrez, O. J. Am. Chem. Soc. 2017, 139, 16126.

铁催化下二芳基锌和芳基格氏试剂的二氟烷基化反应

Iron-Catalyzed Cross-Coupling of Diarylzinc or Aryl Grignard Reagents with Difluoroalkyl Bromides

PDF

补充材料

可视化

摘要/Abstract

引用此文

分享此文

参考文献

相关文章 15

编辑推荐

相关统计

本文评价

[1]	顾晓瑜, 李进, 孙千, 王朝阳. 微量量热法分析锂离子电池热失控过程[J]. 化学学报, 2024, 82(2): 146-151.
[2]	李萍, 杨琪玉, 曾婧, 张然, 陈秋燕, 闫飞. 氟掺杂对可逆固体氧化物电池性能的影响及相关动力学研究[J]. 化学学报, 2024, 82(1): 36-45.
[3]	张凯, 武晓君. 具有室温铁磁性的二维Janus钛硫属化物^★[J]. 化学学报, 2023, 81(9): 1142-1147.
[4]	周俊粮, 赵振新, 武庭毅, 王晓敏. 多功能磷化铁碳布(FeP/CC)中间层高效催化多硫化物实现锂硫电池的高容量与高稳定性[J]. 化学学报, 2023, 81(4): 351-358.
[5]	高丰琴, 刘洋, 张引莉, 蒋育澄. 羧基功能化Fe₃O₄固定化酶反应器的构筑及性能研究[J]. 化学学报, 2023, 81(4): 338-344.
[6]	韩明亮, 徐丽华. 过渡金属催化的硫酯的交叉偶联反应研究进展[J]. 化学学报, 2023, 81(4): 381-392.
[7]	刘春梅, 高燕均, 陈鹏亮. 直接甲酸钠/铁氰化钾微流体燃料电池性能研究[J]. 化学学报, 2022, 80(9): 1256-1263.
[8]	刘俊瑞, 陈晶琳, 杨杰, 许肖锋, 李若男, 黄有桂, 陈少华, 叶欣, 王维. 钾位铈掺杂黄钾铁矾的磷吸附特性及机理研究^※[J]. 化学学报, 2022, 80(4): 476-484.
[9]	张芬, 李霄琪, 韩世国, 邬发发, 刘希涛, 孙志华, 罗军华. 大尺寸二维卤化物钙钛矿铁电晶体的生长及偏振光电探测性能研究^※[J]. 化学学报, 2022, 80(3): 237-243.
[10]	李尚钊, 欧阳振武, 邹俊杰, 王东阳, 许斌, 邓亮. 氮杂环卡宾配位的单核型一价铁硫酚基配合物[J]. 化学学报, 2022, 80(3): 272-276.
[11]	张容, 柳江萍, 朱子怡, 陈淑妹, 王飞, 张健. 二茂铁功能化的两例镉金属有机框架材料的合成、结构和表征^※[J]. 化学学报, 2022, 80(3): 249-254.
[12]	郭湾, 胡聪意, 甄淑君, 黄承志, 李原芳. 铁基金属有机凝胶衍生的三氧化二铁纳米片用于光芬顿降解罗丹明B[J]. 化学学报, 2022, 80(12): 1583-1591.
[13]	杨思明, 刘爱荣, 刘静, 刘钊丽, 张伟贤. 硫化纳米零价铁研究进展: 合成、性质及环境应用[J]. 化学学报, 2022, 80(11): 1536-1554.
[14]	张竹涵, 蒋峰景, 吴珂科, 申鹏. 基于3D固态负极的铁铅单液流电池研究[J]. 化学学报, 2022, 80(1): 56-62.
[15]	滑熠龙, 李冬涵, 顾天航, 王伟, 李若繁, 杨建平, 张伟贤. 纳米零价铁富集水溶液中铀的表面化学及应用展望[J]. 化学学报, 2021, 79(8): 1008-1022.